GENEWATCH
 
GIVE THEM AN INCH...
By Michael Siciliano
 

I was scheduled to appear as an expert witness at Becky McClain's trial against Pfizer. My testimony was to be that the symptoms of Mrs. McClain's illness were consistent with her being exposed to a virus being worked on in the laboratory. In the judge's opinion, the lack of physical evidence relating any such exposure to the disease was considered insufficient and the related count was thrown out.  However, I was confident that I could testify on biosafety issues-I am well practiced in the art of biosafety, having run a molecular genetics and cell biology laboratory for over 35 years in which biosafety considerations were carefully met. I did have concern about how flawed Pfizer's biosafety practices could really be.

Pfizer claimed that Mrs. McClain was terminated for not returning to work after she took a leave due to her illness; Mrs. McClain said that she was fearful about returning to work because of the lax and dangerous biosafety practices at Pfizer. I could not imagine that Pfizer was lax in that area because a former Pfizer research director I knew assured me that the Standard Operating Procedures for Pfizer were to follow the National Institutes of Health guidelines for biosafety when dealing with recombinant DNA activity.

I was shocked to learn that Pfizer's own guidelines for appropriate procedure, as well as NIH guidelines, were not followed in Mrs. McClain's department and that she had a real basis for her fear in returning to work.  In some cases the lack of safety standards appeared to be due to ignorance and in others it appeared to be due to an apparent flagrant disregard for world-recognized appropriate procedure.

The problem proved to be systemic: Pfizer's head of biosafety, Dr. Eric Utt, admitted that no risk assessment had been conducted on the potentially dangerous lentivirus experiment conducted in Mrs. McClain's workspace-or, in fact, for lentivirus experiments in general. Why would no risk assessment be done when it is such a fundamental procedure before initiating any such experiments with potentially biohazardous material as a lentivirus? Dr. Utt answered that such assessment is already done on the kits they get that contain the reagents for the experiment.  This is a monstrously frightening statement, coming from one at such a lofty position in the organization with respect to biosafety.

So what's the big deal?

The lentivirus which McClain was exposed is a retrovirus. This means its genetic code is in the form of RNA rather than DNA. The RNA is in a "coat" which enables it to attach to a broad spectrum of mammalian cells and become engulfed in the cell. As described by the late brilliant Nobel-prize winning molecular geneticist Howard Temin, the virus has a gene (called reverse transcriptase or RET) which enables it to go backwards in the genetic paradigm. Normally, the DNA code for a gene creates an RNA message which directs the formation of the protein specified by the gene. RET makes it possible to go backwards, making DNA from the RNA. The viral DNA can then be inserted into the DNA of the chromosomes. New gene insertion with long term effects becomes possible, depending on what the virus has been designed to do. The gene therapy possibilities are intoxicating to drug companies and biomedical research. We can expect increased intensity in this field in the near future. 

Temin suggested that making the virus replication deficient might be a safe form of gene therapy. However, we have now learned that a replication deficient virus, such as what Pfizer was using, can recombine with other viruses in its environment, or in the cell into which it is transduced, to become competent. From there it can replicate itself millions of times and create severe disease scenarios.

That is not the only problem these genetically engineered viruses can cause. Upon insertion into host cell DNA the virus can cause mutations at the sites of insertion that lead to cancer. These events, including recovery of replication competence, have been described in monkeys and in humans undergoing initial gene therapies, resulting in approximately 30% of subjects treated dying of lymphoma.

In a proper Risk Assessment, one needs to determine not only the genes in the virus being used, but also the spectrum of infectivity of its coat as well as the concentration of the virus being used. It is also necessary to consider the mammalian cells being transduced. They may be harboring other viruses in various cellular regions or have their sequences integrated into its chromosomes. These are all targets for recombination which can generate a replication-competent virus. Such issues cannot be addressed in a commercially available reagent kit disclaimer since the specifics of the virus, its concentration, and cells into which they are being transduced are not considered.  These parameters need to be articulated in a Risk Assessment sent to the Institutional Biosafety Committee, which needs to give final approval for the experiment depending on its perceived risk/benefit ratio and indicating the conditions under which such an experiment can be performed.  That is the only acceptable NIH approved procedure.

Later I had the opportunity to speak with Dr. Utt. I told him that he needed to know that his Risk Assessment was not consistent with NIH guidelines on biosafety. He smiled and said that Pfizer was not bound to follow NIH guidelines.

He was right. An academic institution must follow NIH rules or lose their funding for their projects-all the projects at the institution. Drug companies don't get NIH funding, so their guidelines are as effective as traffic signs in Italy: mere suggestions.

The time has come for new law. The number of biotech workers is growing, and we can expect increased involvement from big pharma. Workers need legal rights to obtain disclosure of the identity of the biological agents to which they are exposed in order to obtain directed medical care. Unless biotechnology labs are brought under appropriate regulation, severe threats persist for the welfare of workers in the industry as well as the general public.

 

Michael J. Siciliano, Ph.D., D.Sc.(hon), was Kenneth D. Muller Professor of Tumor Genetics (Ret.) at The University of Texas M.D. Anderson Cancer Center.

 
 
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